Abstract
Previous diffusion tensor imaging (DTI) studies confirmed the vulnerability of frontal callosal fibers to normal aging. The present study extended this examination systematically to other prefrontal white matter regions. Structural magnetic resonance imaging and DTI datasets were acquired from 69 healthy subjects aged 22–84 years. The prefrontal white matter was parcellated into several anatomical sub-regions: medial and lateral orbitofrontal white matter, dorsolateral prefrontal white matter, and medial prefrontal white matter, using reliable DTI-tractography protocols. Tract-specific characteristics were calculated using Matlab. Regression models were used to determine the relationship between age and structural integrity of white matter tracts. The results of our study demonstrate regional age-related changes in the prefrontal white matter tracts of the human brain. This study was cross-sectional and therefore additional longitudinal studies are needed to confirm our findings.
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Abe O, Aoki S, Hayashi N, Yamada H, Kunimatsu A, Mori H, Yoshikawa T, Okubo T, Ohtomo K (2002) Normal aging in the central nervous system: quantitative MR diffusion-tensor analysis. Neurobiol Aging 23:433–441
Aboitiz F, Rodríguez E, Olivares R, Zaidel E (1996) Age-related changes in fibre composition of the human corpus callosum: sex differences. Neuroreport 7:1761–1764
Allen JS, Bruss J, Brown CK, Damasio H (2005) Normal neuroanatomical variation due to age: the major lobes and a parcellation of the temporal region. Neurobiol Aging 26:1245–1260
Bartzokis G (2004) Age-related myelin breakdown: a developmental model of cognitive decline and Alzheimer’s disease. Neurobiol Aging 25:5–18
Barzokis G, Beckson M, Lu PH, Nuecherterlein KH, Edwards N, Mintz J (2001) Age related changes in frontal and temporal lobes in men. Arch Gen Psychiatry 58:461–465
Bhagat YA, Beaulieu C (2004) Diffusion anisotropy in subcortical white matter and cortical gray matter: changes with aging and the role of CSF suppression. J Magn Reson Imaging 20:216–227
Burgmans S, van Boxtel MP, Gronenschild EH, Vuurman EF, Hofman P, Uylings HB, Jolles J, Raz N (2010) Multiple indicators of age-related differences in cerebral white matter and the modifying effects of hypertension. Neuroimage 49(3):2083–2093
Burzynska AZ, Preuschhof C, Bäckman L, Nyberg L, Li SC, Lindenberger U, Heekeren HR (2010) Age-related differences in white matter microstructure: region-specific patterns of diffusivity. NeuroImage 49:2104–2112
Courchesne E, Chisum H, Townsend J, Cowles A, Covington J, Egaas B, Harwood M, Hinds S, Press G (2000) Normal brain development and aging: quantitative analysis at in vivo MR Imaging in healthy volunteers. Radiology 216:672–682
Cowell PE, Sluming VA, Wilkinson ID, Cezayirli E, Romanowski CA, Webb JA, Keller SS, Mayes A, Roberts N (2007) Effects of sex and age on regional prefrontal brain volume in two human cohorts. Eur J Neurosci 25:307–318
Dubois B, Slachevsky A, Litvan I, Pillon B (2000) The FAB: a frontal assessment battery at bedside. Neurology 55:1621–1626
Fjell AM, Walhovd KB, Westlye LT, Østby Y, Tamnes CK, Jernigan TL, Gamst A, Dale AM (2010) When does brain aging accelerate? Dangers of quadratic fits in cross-sectional studies. Neuroimage 50(4):1376–1383
Flechsig P (1901) Developmental myelogenetic localisation of the cerebral cortex in the human subject. Lancet 19:1027–1029
Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198
Fuster JM (2008) The prefrontal cortex. 4th edn. Academic Press, Elsevier, pp 7–59. http://www.elsevierdirect.com/product.jsp?isbn=9780123736444
Ge Y, Grossman RI, Babb JS, Rabin ML, Mannon LJ, Kolson DL (2002) Age-related total gray matter and white matter changes in normal adult brain, part I: volumetric MR imaging analysis. Am J Neuroradiol 23(8):1327–1333
Gogtay N, Giedd JN, Lusk L, Hayashi KM, Greenstein D, Vaituzis AC, Nugent TF 3rd, Herman DH, Clasen LS, Toga AW, Rapoport JL, Thompson PM (2004) Dynamic mapping of human cortical development during childhood through early adulthood. Proc Natl Acad Sci USA 101(21):8174–8179
Good CD, Johnsrude IS, Ashburner J, Henson RN, Friston KJ, Frackowiak RS (2001) A voxel-based morphometric study of aging in 465 normal adult human brains. Neuroimage 14:21–36
Grieve SM, Clark CR, Williams LM, Peduto AJ, Gordon E (2005) Preservation of limbic and paralimbic structures in aging. Hum Brain Mapp 25:391–401
Grieve SM, Williams LM, Paul RH, Clark CR, Gordon E (2007) Cognitive aging, executive function, and fractional anisotropy: a diffusion tensor MR imaging study. Am J Neuroradiol 28:226–235
Gunning-Dixon FM, Brickman AM, Cheng JC, Alexopoulos GS (2009) Aging of cerebral white matter: a review of MRI findings. Int J Geriatr Psychiatry 24:109–117
Hasan KM, Kamali A, Iftikhar A, Kramer LA, Papanicolaou AC, Fletcher JM, Ewing-Cobbs L (2009) Diffusion tensor tractography quantification of the human corpus callosum fiber pathways across the lifespan. Brain Res 1249:91–100
Hasan KM, Kamali A, Abid H, Kramer LA, Fletcher JM, Ewing-Cobbs L (2010) Quantification of the spatiotemporal microstructural organization of the human brain association, projection and commissural pathways across the lifespan using diffusion tensor tractography. Brain Struct Funct 214(4):361–73
Hsu JL, Leemans A, Bai CH, Lee CH, Tsai YF, Chiu HC, Chen WH (2008) Gender differences and age-related white matter changes of the human brain: a diffusion tensor imaging study. NeuroImage 39:566–577
Jernigan T, Archibald S, Fennema-Notestine C, Gamst A, Stout J, Bonner J, Hesselink J (2001) Effects of age on tissues and regions of the cerebrum and cerebellum. Neurobiol Aging 22:581–591
Jiang H, van Zijl PC, Kim J, Pearlson GD, Mori S (2006) DtiStudio: resource program for diffusion tensor computation and fiber bundle tracking. Comput Methods Programs Biomed 81:106–116
Jones DK (2004) The effect of gradient sampling schemes on measures derived from diffusion tensor MRI: a Monte Carlo study. Magn Reson Med 51:807–815
Kaufer DI (2007) The dorsolateral and cingulate cortex. In: Miller BL, Cummings JL (eds) The human frontal lobes. The Guilford press, New York, pp 44–58
Kringelbach ML, Rolls ET (2004) The functional neuroanatomy of the human orbitofrontal cortex: evidence from neuroimaging and neuropsychology. Prog Neurobiol 72:341–372
Landman BA, Farrell JA, Jones CK, Smith SA, Prince JL, Mori S (2007) Effects of diffusion weighting schemes on the reproducibility of DTI-derived fractional anisotropy, mean diffusivity, and principal eigenvector measurements at 1.5T. NeuroImage 36:1123–1138
Lebel C, Walker L, Leemans A, Phillips L, Beaulieu C (2008) Microstructural maturation of the human brain from childhood to adulthood. NeuroImage 40:1044–1055
Mackey S, Petrides M (2009) Architectonic mapping of the medial region of the human orbitofrontal cortex by density profiles. Neuroscience 159(3):1089–1107
Madden DJ, Bennett IJ, Song AW (2009) Cerebral white matter integrity and cognitive aging: contributions from diffusion tensor imaging. Neuropsychol Rev 19:415–435
Malykhin NV, Bouchard TP, Ogilvie CJ, Coupland NJ, Seres P, Camicioli R (2007) Three-dimensional volumetric analysis and reconstruction of amygdala and hippocampal head, body and tail. Psychiatry Res: Neuroimaging 155:155–165
Malykhin N, Concha L, Seres P, Beaulieu C, Coupland NJ (2008) Diffusion tensor imaging tractography and reliability analysis for limbic and paralimbic white matter tracts. Psychiatry Res: Neuroimaging 164:132–142
Marner L, Nyengaard JR, Tang Y, Pakkenberg B (2003) Marked loss of myelinated nerve fibers in the human brain with age. J Comp Neurol 462:144–152
Mattis S (1988) Dementia rating scale professional manual. Psychological Assessment Resources, Odessa
McLaughlin NC, Paul RH, Grieve SM, Williams LM, Laidlaw D, DiCarlo M, Clark CR, Whelihan W, Cohen RA, Whitford TJ, Gordon E (2007) Diffusion tensor imaging of the corpus callosum: a cross-sectional study across the lifespan. Int J Dev Neurosci 25:215–221
Meier-Ruge W, Ulrich J, Bruhlmann M, Meier E (1992) Age-related white matter atrophy in the human brain. Ann N Y Acad Sci 673:260–269
Michielse S, Coupland NJ, Camicioli R, Carter R, Seres P, Sabino J, Malykhin N (2010) Selective effects of aging on brain white matter microstructure: a diffusion tensor imaging tractography study. NeuroImage 52:1190–1201
Ongür D, Ferry AT, Price JL (2003) Architectonic subdivision of the human orbital and medial prefrontal cortex. J Comp Neurol 460(3):425–449
Orzhekhovskaia NS (1975) Comparative study of formation of the frontal cortex of the brain of monkeys and man in ontogenesis. Arkh Anat Gistol Embriol 68(3):43–49
Pagani E, Agosta F, Rocca MA, Caputo D, Filippi M (2008) Voxel-based analysis derived from fractional anisotropy images of white matter volume changes with aging. NeuroImage 41:657–667
Pfefferbaum A, Mathalon DH, Sullivan EV, Rawles JM, Zipursky RB, Lim KO (1994) A quantitative magnetic resonance imaging study of changes in brain morphology from infancy to late adulthood. Arch Neurol 51:874–887
Pfefferbaum A, Sullivan EV, Hedehus M, Lim KO, Adalsteinsson E, Moseley M (2000) Age-related decline in brain white matter anisotropy measured with spatially corrected echo-planar diffusion tensor imaging. Magn Reson Med 44:259–268
Price JL (2007) Definition of the orbital cortex in relation to specific connections with limbic and visceral structures and other cortical regions. Ann N Y Acad Sci 1121:54–71
Rajkowska G, Goldman-Rakic PS (1995) Cytoarchitectonic definition of prefrontal areas in the normal human cortex: I. Remapping of areas 9 and 46 using quantitative criteria. Cereb Cortex 5:307–322
Raz N, Rodrigue KM (2006) Differential aging of the brain: patterns, cognitive correlates and modifiers. Neurosci Biobehav Rev 30:730–748
Raz N, Kennedy KM (2009) A systems approach to the aging brain: neuroanatomical changes, their modifiers, and cognitive correlates. In: Jagust W, D’Esposito M (eds) Imaging the aging brain. Oxford University Press, New York, pp 43–70
Raz N, Gunning FM, Head D, Dupuis JH, McQuain J, Briggs SD, Loken WJ, Thornton AE, Acker JD (1997) Selective aging of the human cerebral cortex observed in vivo: differential vulnerability of the prefrontal gray matter. Cereb Cortex 7:268–282
Raz N, Gunning-Dixon F, Head D, Rodrigue KM, Williamson A, Acker JD (2004) Aging, sexual dimorphism, and hemispheric asymmetry of the cerebral cortex: Replicability of regional differences in volume. Neurobiol Aging 25:377–396
Resnick S, Lamar M, Driscoll I (2007) Vulnerability of the orbitofrontal cortex to age-associated structural and functional brain changes. Ann N Y Acad Sci 1121:562–575
Salat DH, Tuch DS, Greve DN, van der Kouwe AJ, Hevelone ND, Zaleta AK, Rosen BR, Fischl B, Corkin S, Rosas HD, Dale AM (2005a) Age-related alterations in white matter microstructure measured by diffusion tensor imaging. Neurobiol Aging 26:1215–1227
Salat DH, Tuch DS, Hevelone ND, Fischl B, Corkin S, Rosas HD, Dale AM (2005b) Age-related changes in prefrontal white matter measured by diffusion tensor imaging. Ann N Y Acad Sci 1064:37–49
Salat DH, Greve DN, Pacheco JL, Quinn BT, Helmer KG, Buckner RL, Fischl B (2009) Regional white matter volume differences in nondemented aging and Alzheimer’s disease. NeuroImage 44(4):1247–1258
Schmahmann JD, Pandya D (2006) Fiber pathways of the brain. Oxford University Press, New York, p 654
Smith CD, Chebrolu H, Wekstein DR, Schmitt FA, Markesbery WR (2007) Age and gender effects on human brain anatomy: a voxel-based morphometric study in healthy elderly. Neurobiol Aging 28:1075–1087
Snook L, Paulson LA, Roy D, Phillips L, Beaulieu C (2005) Diffusion tensor imaging of neurodevelopment in children and young adults. NeuroImage 26:1164–1173
Song SK, Sun SW, Ju WK, Lin SJ, Cross AH, Neufeld AH (2003) Diffusion tensor imaging detects and differentiates axon and myelin degeneration in mouse optic nerve after retinal ischemia. NeuroImage 20:1714–1722
Stadlbauer A, Salomonowitz E, Strunk G, Hammen T, Ganslandt O (2008) Age-related degradation in the central nervous system: assessment with diffusion-tensor imaging and quantitative fiber tracking. Radiology 247:179–188
Stuss DT, Alexander MP (2000) Executive functions and the frontal lobes: a conceptual view. Psychol Res 63:289–298
Sullivan EV, Pfefferbaum A (2006) Diffusion tensor imaging and aging. Neurosci Biobehav Rev 30:749–761
Sullivan EV, Adalsteinsson E, Hedehus M, Ju C, Moseley M, Lim KO, Pfefferbaum A (2001) Equivalent disruption of regional white matter microstructure in ageing healthy men and women. Neuroreport 12:99–104
Sullivan EV, Adalsteinsson E, Pfefferbaum A (2006) Selective age-related degradation of anterior callosal fiber bundles quantified in vivo with fiber tracking. Cereb Cortex 16:1030–1039
Sullivan EV, Rohlfing T, Pfefferbaum A (2010) Quantitative fiber tracking of lateral and interhemispheric white matter systems in normal aging: Relations to timed performance. Neurobiol Aging 31:464–481
Tang Y, Nyengaard JR, Pakkenberg B, Gundersen HJ (1997) Age-induced white matter changes in the human brain: a stereological investigation. Neurobiol Aging 18:609–615
Uylings HB, Sanz-Arigita EJ, de Vos K, Pool CW, Evers P, Rajkowska G (2010) 3-D cytoarchitectonic parcellation of human orbitofrontal cortex correlation with postmortem MRI. Psychiatry Res 183(1):1–20
Voineskos AN, Rajji TK, Lobaugh NJ, Miranda D, Shenton ME, Kennedy JL, Pollock BG, Mulsant BH (2010) Age-related decline in white matter tract integrity and cognitive performance: A DTI tractography and structural equation modeling study. Neurobiol Aging. doi:10.1016/j.neurobiolaging.2010.02.009 (Epub ahead of print)
Wakana S, Caprihan A, Panzenboeck MM, Fallon JH, Perry M, Gollub RL, Hua K, Zhang J, Jiang H, Dubey P, Blitz A, van Zijl P, Mori S (2007) Reproducibility of quantitative tractography methods applied to cerebral white matter. NeuroImage 36:630–634
Watson D, Weber K, Assenheimer JS, Clark LA, Strauss ME, McCormick RA (1995) Testing a tripartite model: I. Evaluating the convergent and discriminant validity of anxiety and depression symptom scales. J Abnorm Psychol 104:3–14
Yesavage JA (1988) Geriatric Depression Scale. Psychopharmacol Bull 24(4):709–711. http://www.ncbi.nlm.nih.gov/pubmed/3249773
Acknowledgments
This work was supported by the Canadian Institutes of Health Research (CIHR MOP 64413 to NC, CIHR MOP 67132 to RC). Personnel support: Alberta Heritage Foundation for Medical Research (AHFMR) (NC); Office of the Provost and Vice-President (Academic), University of Alberta (SV).
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Malykhin, N., Vahidy, S., Michielse, S. et al. Structural organization of the prefrontal white matter pathways in the adult and aging brain measured by diffusion tensor imaging. Brain Struct Funct 216, 417–431 (2011). https://doi.org/10.1007/s00429-011-0321-1
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DOI: https://doi.org/10.1007/s00429-011-0321-1